System for automating scientific and engineering experimentation

ABSTRACT

A system for automating experimentation is disclosed. The system comprises an automated experimentation platform (AEP) for automating research, development, and engineering experimentation processes and work and a generalized exchange module (GEM) for automating data exchanges between the AEP and external software applications, devices, or the instrument control programs (ICPs) controlling the devices; a generalization of the exchange module enables all automated data exchanges to be generic. Through the use of the automated experimentation platform (AEP) and the generalized exchange module (GEM), the automation can be adapted to any targeted external software application, device or a devices&#39; controlling software program.

FIELD OF THE INVENTION

The present invention relates generally to automating research,development, and engineering experimentation processes and work and morespecifically to providing a system for automated experimentation.

BACKGROUND OF THE INVENTION

The execution steps in most research, development, and engineeringexperiments generally involve manual operations carried out onunconnected technology platforms. The scientist or engineer works inwhat are essentially isolated technology islands with manual operationsproviding the only bridges. To illustrate, when there is a StandardOperating Practice (SOP) Guide for the experimental work, it is often anelectronic document, for example in Microsoft Word. The experimentalplan (Step 1) within the SOP Guide has to be transferred to the targetdevice (instrument, instrument platform, or component module forexecution (Step 2) by manually re-keying the experiment into thedevice's instrument control program (ICP)—the device's controllingapplication software. In a few cases the statistical analysis of results(Step 3a) can be done within the ICP, but it is most often done within aseparate statistical analysis software package or spreadsheet programsuch as Microsoft Excel. This also requires manually transferring theresults data from the ICP to the analysis software package. Reporting ofresults (Step 3b) is usually carried out in Microsoft Word, andtherefore requires the manual transfer of all results tables and graphsfrom the separate statistical analysis software package. The manualoperations within the general execution sequence steps are presentedbelow. The isolated technology islands are illustrated in FIGS. 1 and 2.

FIG. 1 illustrates the manual tools and operations involved in carryingout a research and development experiment. In this work a statisticalexperiment design protocol is first generated, via step 12. Thisprotocol is developed manually and off-line using nonvalidated toolssuch as Microsoft Word. The protocol then must be approved, once againmanually and off-line, via step 14. Next, sample amounts are calculatedusing non-validated tools such as Microsoft Excel, via step 16.Thereafter the samples are prepared, via step 18 and the experiment isrun on a target device, via step 20, for example, a high-performanceliquid chromatograph (HPLC). Running the experiment requires manuallyre-constructing the statistical design within the target device's ICP.When this software does not exist, or does not allow for full instrumentcontrol, the experiment must be carried out in a fully manual mode bymanually adjusting instrument settings between experiment runs.

FIG. 2 illustrates the manual tools and operations involved in analyzingthe data and reporting the results of the research and developmentexperiment, via step 22. The analysis and reporting of data isaccomplished by first statistically analyzing and interpreting the data,off-line, using non-validated tools such as Microsoft Excel. Next, it isdetermined whether or not there is a need for more experiments, possiblyusing off-line generic design of experiments (DOE) software, via step24. Then, data are entered and a report is written, via step 26.Finally, the report is archived, via step 28. As is seen from the above,the research, development, and engineering experimentation processinvolves a series of activities that are currently conducted in separate“technology islands” that require manual data exchanges among the toolsthat are used for each activity. However, until now, no overarchingautomation technology exists that brings together all the individualactivities under a single integrated-technology platform that is adaptedto multiple devices and data systems.

Method validation activities encompass the planning and experimentalwork involved in verifying the fitness of an analytical method for itsintended use. These activities are often captured in company StandardOperating Procedure (SOP) documents that usually incorporate Food andDrug Administration (FDA) and International Conference on Harmonization(ICH) requirements and guidances. Method validation SOP documentsinclude a description of all aspects of the method validation work foreach experiment type (e.g. accuracy, linearity) within a framework ofthree general execution sequence steps: (1) experimental plan, (2)instrumental procedures, and (3) analysis and reporting of results. Theindividual elements within these three general steps are presentedbelow.

Step 1: Generate Experimental Plan

Select experiment type

Select target instrument

Define study variables:

-   -   analyte concentrations    -   instrument parameters    -   environmental parameters

Specify number of levels per variable

Specify number of preparation replicates per sample

Specify number of injections per preparation replicate

Integrate standards

Include system suitability injections

Define Acceptance Criteria

Step 2: Construct Instrumental Procedures

Define required transformations of the experiment plan into the nativefile or data formats of the instrument's controlling ICP software(construction of Sample Sets and Method Sets or Sequence and Methodsfiles).

-   -   Specify number of injections (rows)    -   Specify type of each injection (e.g., sample, standard)    -   Define required modifications to the analytical method        (robustness)

Step 3: Analyze Data and Report Results

Specify analysis calculations and report content and format

Carry out numerical analyses

Compare analysis results to acceptance criteria (FDA & ICH requirements)

Specify graphs and plots that should accompany the analysis

Construct graphs and plots

Compile final report

The execution steps in analytical method validation generally involvemanual operations carried out on unconnected technology platforms. Toillustrate, an SOP Guide for the validation of an HPLC analytical methodis often an electronic document in Microsoft Word. The experimental plan(Step 1) within the SOP Guide has to be transferred to the HPLCinstrument for execution (Step 2) by manually re-keying the experimentinto the instrument platform's ICP—in the case of an HPLC this istypically referred to as a chromatography data system (CDS). In a fewcases the statistical analysis of results (Step 3) can be performedwithin the CDS, but it is most often carried out within a separatestatistical analysis software package or spreadsheet program such asMicrosoft Excel. This also requires manually transferring the resultsdata from the CDS to the analysis software package. Reporting of results(Step 3) is usually carried out in Microsoft Word, and thereforerequires the manual transfer of all results tables and graphs from theseparate statistical analysis software package. The manual operationswithin the three general execution sequence steps are presented below.

Step 1—Experimental Plan

Validation plan developed in Microsoft Word.

Experimental design protocol developed in off-line DOE software.

Step 2—Instrumental Procedures

Manually build the Sequences or Sample Sets in the CDS.

Raw peak (x, y) data reduction calculations performed by the CDS (e.g.peak area, concentration).

Step 3a—Statistical Analysis

Calculated results manually transferred from the CDS to Microsoft Excel.

-   -   Statistical analysis usually carried out manually in Microsoft        Excel.

Some graphs generated manually in Microsoft Excel, some obtained fromthe CDS.

Step 3b—Reporting of Results

Reports manually constructed from template documents in Microsoft Word.

Graphs and plots manually integrated into report document.

Prior art systems are known in this area, but they do not address theoverarching problem of removing the manually intensive steps required tobridge the separate technology islands. Relevant prior art that has beendiscovered by applicants is described herein below.

PRIOR ART

U.S. Pat. No. 5,369,566, Pfost et al.

This patent is directed to a method of programming a programmablecontroller in a manner by which a variety of menus, options, orquestions seeking limited parameter answers.

The patent also relates to an analytical chemistry processing center andclinical and research laboratory workstation capable of performing thefunctions of several individual instruments and, more particularly, toan automated laboratory workstation useful in the performance ofnumerous chemical, biochemical, and biological assays and reactions.

US 20020156792, Gombocz et al.

This published application is directed to a system, method, computerprogram, and computer program product for the provision of interactive,unified, functionality for data acquisition, management, viewing, andanalysis.

US 20030050763, Arrit et al.

This published application is directed to a referential and relationaldatabase software comprising (a) programmable access for imputation oflaboratory operating procedures; (b) communication between said softwareand testing instrumentation, said software extracting information fromsaid instrumentation; (c) automatic population of designated databasefields from said information; (d) manual population of designateddatabase fields; and (e) review of information.

U.S. Pat. No. 6,581,012 B1, Aryev et al.

This patent is directed to an integrated clinical laboratory softwaresystem for testing a specimen.

WO 2004/038602, A1, Baker

This international application is directed to computer software basedsystem that provides for automated processing of raw spectral data, datastandardization, reduction to data to modeling form, and unsupervisedand supervised model building, visualization, analysis, and prediction.

US 2003/0200004, Renner

This published application is directed to a system for automation oftechnical processes and/or experiments having a measurement unit and acontrol unit which are connected to sensors and actuators of the processor of the experimental unit via measurements and control channels,having at least one library that contains visualization objects andcontrol modules, and having software that manages the system.

US 2004/0034478, Yung et al.

This published application is directed to a computer software basedsystem for integrating laboratory instrumentation and applications toprovide a uniform control and coordination architecture under a commoninterface.

WO 2004/0148291 A1, Dorset Jr.

This international application is directed to models and apparatus,including computer program apparatus, representing a generic experimentmodel or class adaptable to a researcher-defined set of variables, forprocessing data from chemical experimentation.

US 20050080588, Kobayashi et al.

This published application is directed to providing an object of thepresent invention is to provide an object guide customizable measuringinstrument that enables a user to execute an operation guide filecreated with use of a versatile language according to a desired purposeof use, and automatically operates the measurement instrument whilemaking the operation guide displayable by execution of the operationguide file.

Accordingly, none of these references provide for a system or method toaddress the manually intensive operations associated with research,development, and engineering experimental work.

To summarize, research, development, and engineering experiments areoften carried out in isolated technology islands. Each island can haveits own hardware, with or without controlling software, and eachsoftware system can have its own data content and data structure.Therefore, carrying out science and engineering experiments can be quitetime consuming and resource intensive, and each manual operationrequired to transfer data across platforms is prone to error. Currently,no overarching automation technology exists that can bring together allthe individual activities and elements under a singleintegrated-technology platform that is adapted to multiple devices,instrument platforms and data systems. As a result, current softwaresolutions are not able to automatically address instrument differencesin order to allow for creation and dissemination of workflow automationtemplates. Therefore, there is a need for a software system thatprovides an overarching automation technology for scientificexperimentation.

The present invention addresses such a need.

SUMMARY OF THE INVENTION

A system for automating experimentation is disclosed. The systemcomprises an automated experimentation platform (AEP) with a devicesetup interface that imports device setup and control definitions andallows user configuration and editing of the definitions, an experimentsetup interface that is dynamically configurable to specific experimenttypes and their target instrument platforms and devices, and allows userfinal configuration and editing of all experiment setup settings, areporting setup interface that dynamically builds reports from data andresults and allows user configuration and editing of the reports, adesign of experiments (DOE) engine that generates statistically validand rigorous scientific experiments and sampling plans tailored to thetarget devices, including any software program for controlling thedevices (ICP); and a generalized exchange module (GEM) for automatingdata exchanges between the AEP and one or more target applications andfor enabling the data exchange to be generic.

Through the use of the automated experimentation platform (AEP) andgeneralized exchange module (GEM) data exchange is automaticallyprovided between the DOE engine and the instrument, device, or ICP; andthrough the generalization of the exchange module the data exchanges canbe adapted to any external software application, instrument, device, orICP. Therefore, configuring of any scientific experiment type, controlof any instrument or device, reporting of any data and results, and dataexchanges between external software applications, instrument platforms,and devices can be achieved by the AEP and GEM automation components ofthe invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the manual tools and operations involved in designinga research, development, or engineering experiment.

FIG. 2 illustrates the manual tools and operations involved in analyzingthe data and reporting the results of a research, development, orengineering experiment.

FIG. 3 illustrates some of the R&D activities in the pharmaceutical drugdevelopment pipeline as one target application area that can be utilizedwith an automated experimentation system in accordance with the presentinvention.

FIG. 4 shows some of the specific pharmaceutical drug developmentpipeline activities that can utilize the automated experimentationsystem as one target application area using an example embodiment inaccordance with the present invention.

FIG. 5 provides automated experimentation platform (AEP) and ageneralized exchange module (GEM) operational flow diagram (1)illustrating XML exchange with a third-party company, and (2) resultingin AEP process flows with an instrument control program (ICP).

FIGS. 6-8 show different software installation configurations of anautomated experimentation system with an ICP.

FIG. 9 illustrates the research, development, or engineering experimentworkflow previously presented in FIG. 1 adapted to an HPLC methodvalidation experiment created within the automated experimentationsystem and automatically transferred to an instrument's ICP.

FIG. 10 illustrates the research, development, or engineering experimentworkflow previously presented in FIG. 2 adapted to an HPLC methodvalidation experiment in which the results are generated by the ICP andautomatically imported into the automated experimentation system forautomated analysis graphing, and reporting.

FIG. 11 shows data flows between the automated experimentation systemsand various experiment instrument devices.

FIG. 12 is a higher-level view of the automated experimentation systemconnecting many common external software applications and ICPs (usingfile-less data exchange) across the drug development pipeline as onetarget application area using an example embodiment.

DETAILED DESCRIPTION Abbreviations and Acronyms

AEP—Automated Experimentation Platform.

CDS—Chromatography Data System. A traditional name for an ICP (seebelow) that controls and handles the data from HPLC and GC instruments(see below).

DOE—design of experiments

GEM—generalized exchange module.

Device—An instrument, piece of equipment, or apparatus. Examples includebut are not limited to analytical instruments, weighing and measurementdevices, sampling and sample handling equipment, and processingequipment.

FDA—United States Food and Drug Administration.

GC—Gas Chromatography. An instrument-based quantitative analyticaltechnique. GC instruments are widely used as research and developmentand quality assurance tools in many industries (e.g. pharmaceuticals,biotechnology, and petrochemicals).

HPLC—High Performance Liquid Chromatography. An instrument-basedquantitative analytical technique. HPLC instruments are widely used asresearch and development and quality assurance tools in many industries(e.g. pharmaceuticals, biotechnology, and petrochemicals).

ICH—International Conference on Harmonization of Technical Requirementsfor Registration of Pharmaceuticals for Human Use.

ICP—instrument control program. The software program that operates adevice.

Programmatic Interface—A software based communication channel thatallows software programs to exchange instructions and data.

SDK—Software Development Kit. An SDK is a published programmaticinterface for a device or a device's ICP.

XML—eXtensible Markup Language. A metalanguage written in SGML thatallows one to design a markup language, used to allow for the easyinterchange of documents on the World Wide Web.

XML Schema—XML Schemas express shared vocabularies and allow machines tocarry out rules made by people. They provide a means for defining thestructure, content and semantics of XML documents.

XSL—eXtensible Stylesheet Language. A language used to construct stylesheets for an XML, consisting of two parts:

1. XSL Transformations (MLT). A language for transforming XML documents.

2. XSL Formatting Objects (XSL FO). XML vocabulary for specifyingformatting semantics.

XSL Transformation—The set of XSL templates applied to XML data totransform it into another format.

XSL File—The file that contains the XML Transformation.

XSD File—XML Schema Definition is a language for specifying the grammarof the markup allowed in an XML file. Such a specification is called aschema and typically has a file extension of XSD.

The present invention relates generally to scientific research,development, and engineering experiments and more specifically toproviding a system for automated experimentation. The followingdescription is presented to enable one of ordinary skill in the art tomake and use the invention and is provided in the context of a patentapplication and its requirements. Various modifications to the preferredembodiments and the generic principles and features described hereinwill be readily apparent to those skilled in the art. Thus, the presentinvention is not intended to be limited to the embodiments shown, but isto be accorded the widest scope consistent with the principles andfeatures described herein.

A system and method in accordance with the present invention providesfor full automation of research, development, and engineeringexperimental work. The present invention provides for:

1. Creating and exchanging device setup and control definitions,experiment type definitions, analysis definitions, reportingdefinitions, and user addressable configuration and control of thedefinitions.

2. An experiment setup interface that dynamically configures to specificexperiment types and their target instrument platforms and devices.

3. Automating data exchange between a design of experiments (DOE)software engine and any targeted software application, instrument,device or ICP.

4. Making the data exchange technology generic and adaptable to anytargeted software application, instrument, device, or ICP.

To describe the features of the present invention in more detail, refernow to the following description in conjunction with the accompanyingFigures.

Overview

An automated experimentation (AE) system in accordance with the presentinvention is a proprietary software platform for automatedexperimentation. In a preferred embodiment, the AE system comprises asoftware program with statistical and mathematical informatics enginesfor:

-   -   Design of experiments (common abbreviations: DOX, DOE)    -   Numerical data analysis    -   2D, 3D, and 4D (trellis) visualization graphics    -   Multiple response optimization    -   Formal reporting

The AE system also includes tools for regulatory (FDA, ICH) compliance,workflow management control, application-specific experimentation, andfile-less data exchange with targeted software applications,instruments, devices, or ICPs.

The AE system exports experiment designs to targeted softwareapplications, instruments, devices, or ICPs as ready-to-run experimentsin the native file and data formats of the target, imports all resultsfrom the target, analyzes and graphs the results, and createspresentation quality reports.

In a currently available example embodiment the AE system's strategicfeatures include:

E-lab Notebook Interface—Document style interface displays reports inHTML windows. Encrypted database file format contains OLE objects forembedding a Microsoft® Word™ document and Microsoft Excel™ workbook.Externally generated graphics can be imported and embedded into allreports.

Full 21 CFR 11 Compliance Support—Includes e-signature controls for alldata entry and exchanges, full audit trail, and event logging.

Analysis and Reporting—Application-specific automated statisticalanalysis, graphing, and reporting.

Acceptance Criteria Testing—Embedded analytics automatically compareactual results with user entered “pass/fail” acceptance criteria.

Workflow Management—Construct and export work templates. Permissions andauthorities control of all work.

In the pharmaceutical and biotechnology industries, current embodimentsof the AE system are utilized in the mission-critical activities withinanalytical R&D, chemical entity development (CED), chemistry development(CRD), process R&D, formula R&D, and manufacturing QA.

FIG. 3 is a diagram that illustrates the R&D activities in thepharmaceutical drug development pipeline that utilize or can benefitfrom statistical design of experiments (DOE) methodologies 100, and socan utilize the AE system in accordance with the present invention. Asis seen, in this type of methodology, first there is a discovery phase102. Next, an exploratory phase 104 takes place. Following completion ofthe exploratory process is a full development phase 106. When the fulldevelopment phase 106 is completed, registration and approval processes108 follow, and then a post marketing phase 110 ends the drugdevelopment activity.

There are several elements in each step 102-110 of the methodology 100.The discovery phase 102 contains a develop and optimize API synthesisprocess element 112 and a characterize drug substance pharmaceuticalproperties process element 114. The exploratory phase 104 includes thedevelop of Phase 1 formula and process 116 and the develop of Phase 1analytical methods process elements 118. The full development phase 106includes the scale-up/optimize API synthesis 120, the develop andoptimize market formula 122, and the develop market formula analyticmethods 124 process elements. Finally, the registration and approval 108and post marketing 110 phases include the post marketing support 126process elements. The use of statistical design of experiments (DOE)methodologies in these phases and process elements acts to speed upproduct development 128.

FIG. 4 shows the specific drug development pipeline activities that canutilize an AE system in accordance with the present invention. Theactivities can be represented as custom application modules of the AEsystem. These application modules can be independently developed andimported directly into the AE system. Currently developed applicationmodules for one embodiment of the AE system are used for the developmentand FDA validation of chromatographic analytical methods used to measurethe amount, purity, and stability of manufactured drug substances(active compounds and impurities) and drug products (finalconsumer-deliverable dosage forms—tablets, capsules, gelcaps, etc.).

More specifically, current application modules and those underdevelopment for one embodiment of the AE system include the following:

A process development module 402, which characterizes API properties anddevelops and optimizes drug substance synthesis and drug productmanufacturing processes.

A method development module 404, which develops and optimizes analyticalmethods used in all drug development pipeline activities.

A formulation development module 406, which develops Phase 1 formula anddevelops and optimizes market formulas.

A stability and quality assurance module 408, which assures shelf-lifestability and ongoing manufacturing quality assurance.

A method validation module 410, which validates the fitness for use ofanalytical methods used in all drug development pipeline activities.

Modules 402, 404, 406, 408 and 410 operate in conjunction with the AEsystem and perform various functions in coordination with themethodologies of discovery 102′, exploration 104′, full development106′, registration and approval 108′ and post-marketing 110′ asdiscussed in FIG. 3 above.

Accordingly, the AE system in an example embodiment of the presentinvention is a software system which utilizes custom application modulesfor the targeted design of experiments and the analysis, graphing,optimization, and reporting of experimental data and results in supportof all drug development pipeline activities.

The AE system imports Device Driver XML files (Device XMLs) generatedoutside of the AE system according to a public Schema, for example anXML schema. Device XMLs contain the data that enables the AE system toset up experiments and address, control, and exchange data with one ormore devices. These XML files contain the instructions that allow the AEsystem to address the existing interface of one or more devices or theircontrolling ICPs.

User generated Device XMLs enable the AE system to address and controlany instrument platform, component module, or device via any public orprivate programmatic interface that the platform module, or devicecontains. No programming need be developed to adapt the existinginterface of an external software program, device, or ICP to the AEsystem.

The AE system utilizes experiment type XML files (Experiment XMLs)generated outside of the AE system according to a public Schema, forexample an AE XML schema. The experiment XMLs contain the data thatenable the AE system to dynamically configure the experiment setupinterface to address the specific experiment type and its targetdevices. The AE system automatically applies an experiment setup builderXSL to the experiment XML and the device XML to generate an experimentsetup XML that complies with the AE XML Schema. No programming need bedeveloped to adapt the experiment type to the AE system. An AE graphicaluser interface (GUI) builder transforms experiment type settingsdescriptions and device descriptions into AE's dynamically configurableAE DOE GUI. The GUI displays all experiment type settings along withdevice control points, constraints, and graphical images of each controlpoint, for final refinement. The AE DOE GUI enables construction ofstatistically designed experiments for automatic execution on the deviceusing the final experiment type and device settings description.

The AE system utilizes analysis template XML files (Analysis XMLs)generated outside of the AE system according to a public Schema, forexample an AE XML schema. The analysis XMLs contain the data thatenables the AE system to dynamically select and sequence the analysisroutines from its internal analysis library that are applied to data andresults to generate an analysis results set template specific to theexperiment type, the user requirements, and the area of application. Theanalysis results set can be automatically available to any report byincluding it into the report XML. No programming need be developed toadapt analysis templates to the AE system. An AE analysis buildertransforms analysis routine and sequence settings descriptions into AE'sdynamically configurable data analyzer GUI. The GUI displays all routineand sequence settings for final refinement. The data analyzer GUIenables automatic data analysis on the AE System using the finalanalysis settings description.

The AE system utilizes report template XML files (Report XMLs) generatedoutside of the AE system according to a public Schema, for example a AEXML schema. The Report XMLs contain the data that enables the AE systemto dynamically configure the reporting engine to generate a reportspecific to the experiment type, the user requirements, and the area ofapplication. No programming need be developed to adapt report templatesto the AE system. An AE report builder transforms analysis report dataand results complement and sequence settings descriptions into AE'sdynamically configurable reporter GUI. The GUI displays all complementand sequence settings for final refinement. The reporter GUI enablesautomatic report generation on the AE System using the final reportsettings description.

The public XML schema enables the user to update, add to, remove, orotherwise modify the device XMLs, experiment XMLs, analysis XMLs, andreport XMLs created for external software applications, instrumentplatforms, devices, or ICPs at any time to dynamically address changesto the target application platform, device, or ICP.

In addition, in a preferred embodiment, the AE system includes a varietyof plug-in application modules—each of which generates specific types ofstatistically-based experiment designs as directed by experiment typeXMLs and device XMLs, and executes the associated analysis, graphing,optimization, and reporting of the experiment's results, as directed byanalysis XMLs and report XMLs. The user could configure and direct theapplication modules, for example, in a preferred embodiment, byconstructing device XMLs, experiment XMLs, analysis XMLs, and reportXMLs, and operate the application module tools through a series ofrule-based wizards.

AE system application modules can address a wide variety of differentapplication areas. For example, one application module is used forchromatographic analytical instrument method development while anotheris used for synthetic chemistry process development.

The device XMLs of the AE system also preferably contain the data thatenables the AE to address, control, and exchange data with variousindependently conceived and separately designed target softwareapplications, instrument platforms, devices, and ICPs via any public orprivate programmatic interface that the target contains.

The AE system in a preferred embodiment is an electronic signature basedsystem for enabling software operations and subroutines and imposingmanagement review and approve loops on user work within the AE system.

The AE system generates statistical experiment designs or userconstructed experiments that can be run on the target instrument,directly or via the instrument's controlling ICP. The AE systemcommunicates the experiments to an instrument's controlling software viafile-less data transfer using the instrument's public or privateprogrammatic interface.

In addition, driver XML files of the AE system contain several layers ofdata regarding constraints on controllable instrument parameters,including:

-   -   Absolute constraints: achievable setting limits.    -   Manager constraints: restrictions on setting limits due to        current state or required practice.    -   Analyst constraints: restrictions based on current experiment        considerations.

The AE system includes an automated experimentation platform (AEP) and ageneralized exchange module (GEM) to provide a unified software platformfor use in automating experiments. To describe the features of GEM andits interaction with the other AE system elements refer now to thefollowing description in conjunction with the accompanying Figures.

Overview—Generalized Exchange Module (GEM)

The generalized exchange module (GEM) is a proprietary software-basedtechnology that enables a software program to dynamically configure itsuser interface and directly control a device and/or directly address thedevice's ICP—whether or not the device's target programmatic interfaceis published in an SDK. The level of control that can be provided by GEMis only limited by the level of device addressability provided by thedevice's programmatic interface. GEM accomplishes this through thefollowing program elements:

GEM XML schema by which users can completely describe for any ICP:

-   -   All controllable elements of a device (modules and sub-modules).    -   Graphical images of each device element.    -   Individual control points of each device element.    -   Dependency relationships between elements and control points of        a device.    -   Constraints (limits and other restrictions) on the allowable        settings of control points.    -   Programmatic commands, addresses, and data paths for controlling        the device.    -   Programmatic commands, addresses, and data paths for retrieving        data from the device.

The following components are utilized in a preferred embodiment of aGEM:

-   -   An ICP importer that transforms an ICP's native device        descriptions into GEM's native data structure.    -   A template importer that transforms experiment type settings        descriptions, analysis settings descriptions, and report        settings descriptions into the AEP's native data structure.    -   A GEM GUI builder that transforms device descriptions into GEM's        dynamically configurable GEM ICP GUI. The GEM ICP GUI displays        all device control points and constraints, including graphical        images of each control point for further refinement and        restriction of the device description.    -   A design of experiment (DOE) exporter that writes the control        point settings of the statistical experiment design or user        constructed experiment to the device.    -   A DOE importer that reads experiment result output data from the        described device.

FUNCTION of GEM

-   -   Transforming an ICP's native device descriptions into GEM's        native data structure.    -   Displaying all device control points and constraints, including        graphical images of each control point via a configurable ICP        user interface.    -   Transforming experiment type, analysis, and reporting settings        descriptions into the AEP's native data structure.    -   Indirect or direct control of a device and/or direct        addressability of the device's ICP whether or not the device's        target programmatic interface is published in an SDK.    -   Writing control point settings to a device or the device's ICP        as ready-to-run experiments in native file and data formats        using file-less data transfer protocols.    -   Reading data from a device or the device's ICP using file-less        data transfer protocols.    -   Converting a user analysis template into a customized analysis        template that auto-completes when the data are automatically        retrieved from a device or the device's ICP via a dynamically        configurable reporting interface.    -   Converting a user reporting template document (Microsoft Word,        RTF, TXT, or HTML) into a customized reporting template that        auto-completes when the data are automatically retrieved from a        device or the device's ICP via a dynamically configurable        reporting interface.        AEP with GEM—Operational Flow Diagram

FIG. 5 presents an AEP and GEM operational flow diagram illustrating (a)XML exchange with a third-party company, and (b) resulting AEP and GEMprocess flows with the instrument company's ICP. Referring to FIG. 5,the flow diagram illustrates that company 1 (S-Matrix Corporation)publishes XML schema for the AE system, via step 502. Then a devicecompany, for example, ABC Corporation, creates experiment, analysis, andreporting settings AE XMLs and device description ICP XMLs according tothe AE system XML schema, via step 504. A GEM process imports device,experiment and analysis templates, via step 505. A GEM process importsreport templates, via step 507. The AEP kernel process carries outdesign, analysis, graphing and optimization, via step 508. The GEMprocess then exports design to the ICP as ready-to-run in ICP's nativedata/file formats, via step 512. The ICP executes the desired experimenton the instrument, and collects results data (results may also bestreamed directly to AE system from the device), via step 514. The ICPthen sends the data and results to the GEM process, which imports thedata and results to the AE system using file-less data exchange, viastep 516. The AEP kernel processes carry out analysis, graphing andoptimization, again via step 508. The AEP process then produces formalreports output in various formats, e.g., PDF, HTML, DOC and TXT, viastep 510.

AEP with GEM—Software Installation Configurations

FIGS. 6-8 show different software installation configurations of the AEsystem (AEP and GEM) with an ICP. FIG. 6 shows a standalone workstationconfiguration 600. The standalone workstation configuration 600 includesa standalone PC 602 linked to the ICP 604, the servers 608 a and 608 b,and the AE system and ICP 400′. FIG. 7 shows a network configuration 700in which the ICP is a Client/Server (C/S) application 704, linked to theICP main server 708 and to another server 706. FIG. 8 shows analternative network configuration 800 in which the ICP is a C/Sapplication 802 and both the AE system and the ICP 400″ are served touser PCs 804 a and 804 b via a client application such as the Citrix®MetaFrame application 808.

Accordingly, AEP and GEM cooperate to automate the formerly manuallyintensive research, development, and engineering experiments. Toillustrate this in more detail refer now to the following discussionwhich is based on one target application area using an exampleembodiment in accordance with the present invention in conjunction withthe accompanying figures.

FIG. 9 illustrates the research, development, or engineering experimentworkflow previously presented in FIG. 1 adapted to an HPLC methodvalidation experiment created within the AE system's central softwareenvironment and automatically transferred to an instrument's ICP. Thisprovides for an automated experiment construction and file-less exportto ICP as ready-to-run in the ICP's native data and file formats. FIG.10 illustrates the research, development, or engineering experimentworkflow previously presented in Figure w, but again carried out withinthe AE system's central software environment. This provides forautomated experiment running and file-less import from ICP as completedresults data sets. The AE system provides an integrated framework tocarry out all the required experiment activities without manuallytranscribing experiments or manually transferring data betweenenvironments.

To maintain data exchange security, the AE system in a preferredembodiment contains a complete 21 CFR 11 (Title 21, Part 11, Code ofFederal Regulations) Regulatory Compliance feature set that enablesmaintenance of regulatory compliance across technology platforms.Example regulatory compliance features include:

-   -   E-signature controls for data exchanges between instrument        platforms.    -   Full audit trail and event logging for all user/software        operations.    -   Automated e-Review and e-Approvals.    -   Full audit trail and event logging for all data events and        reports.

In addition, the AE system provides a complete workflow managementfeature set that enables construction of work templates andsoftware-based administration and control of the work. Example workflowmanagement features include:

-   -   Ability to create and distribute workflow templates.    -   Control of feature/function access with user permissions and        authorities settings.    -   Control of workflow with review and approve e-signing control        loops.    -   E-signature control of all data exchanges with ICPs.

FIG. 11 presents a more complex pharmaceutical experiment platform 1200.The figure illustrates how the AE system 400′″ could integrate threeseparate devices used in an experiment: a tablet press 1202, adissolution tester 1204, and an HPLC System 1206. The tablet press 1202compresses a drug combined with various powdered pharmaceuticalingredients into drug tablets. The dissolution tester 1204 simulates howthe tablets will dissolve in the stomach or intestines. The HPLC 1206samples the dissolution tester 1204 at defined intervals and measuresthe samples to determine how quickly the tablet dissolves and releasesthe drug.

Pharmaceutical scientists use this experiment platform to determine thecombination and formulation of the powdered ingredients and the tabletpress operating conditions which will give them a tablet that releasesthe drug in the required time interval at the required release rate. Theworkflow steps in FIG. 12 involve the following automatedexperimentation operations:

-   -   Experiment design for studying powdered ingredient formula and        process effects (e.g. pressure, speed) generated within the AE        system.    -   Experiment design transferred directly to the ICP controlling        the tablet press 1202 as ready-to-run in the native file and        data formats of the ICP 1206 using file-less data exchange and        e-signature control.    -   Coordinated sample processing design transferred directly to the        ICP controlling the dissolution tester (in this case the CDS) as        ready-to-run in the native file and data formats of the CDS 1206        using file-less data exchange and e-signature control.

In this example the dissolution tester 1204 is controlled by the CDS1206, which also controls the HPLC instrument. Alternatively, the sampleprocessing design could be transferred to an independent ICP controllingthe dissolution tester.

-   -   Coordinated sample testing design transferred directly to the        CDS (the HPLC instrument's ICP) as ready-to-run in the native        file and data formats of the CDS using file-less data exchange        and e-signature control.    -   Experiment results transferred directly from the CDS to the AE        system using file-less data exchange and e-signature control.    -   Fully automated analysis, graphing, and final report development        done within the AE system.    -   Final reports output in the file formats required for the        document archiving system.

FIG. 12 is a higher-level view of the AE system 400″″; here the AEPsystem is shown connecting many common ICPs (using file-less dataexchange) across the drug development pipeline, including those offeredby Argonaut Technologies, Inc. (recently acquired by Biotage AB) 1302,Jasco Inc. 1304, Varian, Inc. 1306, Waters Corporation 1308 andPerkinElmer, Inc. 1310. The figure also shows the AEP system exchangingdata and documents with many common enterprise data management anddocument management software systems, including those offered byNuGenesis Technologies Corporation (recently acquired by WatersCorporation) 1312, VelQuest Corporation 1314, Documentum, Inc. (recentlyacquired by EMC Corporation) 1316 and Scientific Software Inc. (CyberLabproduct—company recently acquired by Agilent Technologies Inc.) 1318.The figure serves to illustrate the power of the generalized dataexchange capabilities that AEP with GEM technology provides.

CONCLUSION

A system and method in accordance with the present invention providesfor full automation of research, development, and engineeringexperimental work and processes.

Through the use of the automated experimentation (AE) system experimentsetup dynamically configures to defined experiment types and theirinvolved instrument platforms and devices, and analysis and reportingdynamically configures to defined requirements and areas of application.Through the use of a generalized exchange module (GEM), definitions ofexperiment types, data analysis, and results reporting for specificexperimental environments or areas of application, and setup and controlof all involved instruments or devices, can be independently developedand imported without the need for programming. Data exchange isautomatically provided between the experimental design, analysis,graphing, optimization, and reporting software engine elements of the AEsystem and targeted external software applications, instruments,devices, or ICPs; the data exchanges can be adapted to any target.

Although the present invention has been described in accordance with theembodiments shown, one of ordinary skill in the art will readilyrecognize that there could be variations to the embodiments and thosevariations would be within the spirit and scope of the presentinvention. Accordingly, many modifications may be made by one ofordinary skill in the art without departing from the spirit and scope ofthe appended claims.

1. A system for automating experimentation comprising: an automatedexperimentation platform (AEP) for automating experimentation processes;and a generalized exchange module (GEM) for automating data exchangesbetween the AEP and one or more target applications and for enabling thedata exchange to be generic.
 2. The system of claim 1 wherein the one ormore target applications can be any of or any combination of externalsoftware applications, devices, or instrument control programs (ICPs).3. The system of claim 1 wherein experimentation processes comprises oneor any combination of research, development, scientific and engineeringprocesses.
 4. The system of claim 1 wherein the generalized exchangemodule (GEM) comprises a plurality of processes for importing data froman independent company and providing the data in a generic language tothe plurality of kernel processes and importing and exporting data froma target application to and from the kernel processes using file-lessdata exchange.
 5. The system of claim 1 wherein the GEM furthercomprises: an instrument control program (ICP) importer that transformsan ICP native device description into the GEM native data structure; atemplate importer that transforms experiment type settings descriptions,analysis settings descriptions, and report settings descriptions intothe AEP native data structure; a GEM graphical user interface (GUI)builder that transforms the GEM native data structure devicedescriptions into a dynamically configurable GEM GUI; an experiment setup GUI that enables construction of experiments for automatic executionusing a physical device description; a design of experiments (DOE)exporter that writes control point settings for the experimenter; and aDOE importer that reads experiment result output data from the device.6. The system of claim 4 wherein the AEP comprises a plurality of kernelprocesses for generating designs, analysis results, and reports andprocesses for constructing and interpreting report templates.
 7. Amethod for automating experimentation comprising: automatingexperimentation processes; and automating data exchange between anautomated experimentation platform (AEP) and one or more targetapplications; and enabling the data exchange to be generic.
 8. Themethod of claim 7 wherein the one or more target applications can be anyof or any combination of external software applications, devices, orinstrument control programs (ICPs).
 9. The method of claim 7 wherein theexperimentation processes comprises one or any combination of research,development, scientific and engineering processes.
 10. The method ofclaim 7 wherein the data exchange automating step includes a pluralityof kernel processes and a plurality of processes for constructing andinterpreting templates.
 11. The method of claim 10 wherein the enablingstep comprises a plurality of processes for importing data and resultsfrom a company and providing the data in a generic language to theplurality of kernel processes and importing and exporting data from atarget application and from the kernel processes using file-less dataexchange.
 12. The method of claim 11 wherein the enabling step comprisesa generalized exchange module (GEM), the GEM further comprising: aninstrument control program (ICP) importer that transforms an ICP nativedevice description into the GEM native data structure; a templateimporter that transforms experiment type settings descriptions, analysissettings descriptions, and report settings descriptions into the AEPnative data structure; a GEM graphical user interface (GUI) builder thattransforms the GEM native data structure device descriptions into adynamically configurable GEM GUI; an experiment set up GUI that enablesconstruction of experiments for automatic execution using a physicaldevice description; a design of experiments (DOE) exporter that writescontrol point settings for the experimenter; and a DOE importer thatreads experiment result output data from the device.
 13. A computerreadable medium containing program instructions for automatingexperimentation comprising: automating experimentation processes; andautomating data exchange between an automated experimentation platform(AEP) and one or more target applications; and enabling the dataexchange to be generic.
 14. The method of claim 13 wherein the one ormore target applications can be any of or any combination of externalsoftware applications, devices, or instrument control programs (ICPs).15. The method of claim 13 wherein the experimentation processescomprises one or any combination of research, development, scientificand engineering processes.
 16. The computer readable medium of claim 13wherein the data exchange automating step includes a plurality of kernelprocesses and a plurality of processes for constructing and interpretingtemplates.
 17. The computer readable medium of claim 13 wherein theenabling step comprises a plurality of processes for importing data froma company and providing the data in a generic language to the pluralityof kernel processes and importing and exporting data and results fromprogram to and from the kernel processes using file-less data exchange.18. The computer readable medium of claim 17 wherein the enabling stepcomprises providing a generalized exchange module (GEM), the GEM furthercomprising: an instrument control program (ICP) importer that transformsan ICP native device description into the GEM native data structure; atemplate importer that transforms experiment type settings descriptions,analysis settings descriptions, and report settings descriptions intothe AEP native data structure; a GEM graphical user interface (GUI)builder that transforms the GEM native data structure devicedescriptions into a dynamically configurable GEM GUI; an experiment setup GUI that enables construction of experiments for automatic executionusing a physical device description; a design of experiments (DOE)exporter that writes control point settings for the experimenter; and aDOE importer that reads experiment result output data from the device.19. A system for automating experimentation comprising: a generalizeddata exchange module (GEM) that (a) imports (i) experiment typedefinitions specific to an experimental environment or area ofapplication, (ii) device setup and control definitions of all involvedinstruments, devices, and ICPs, (iii) analysis template definitionsspecific to individual subroutine complement and sequence requirements,and (iiii) reporting template definitions specific to individual userand area of application requirements; the definitions enabled to beindependently developed according to public data structures without theneed for programming, and (b) automates data exchanges between theautomated experimentation platform (AEP) and various external softwareapplications, instruments, devices, and ICPs and contains a publicinterface for allowing the data exchanges to be generic; and anautomated experimentation platform (AEP) that contains (a) an experimentsetup interface that dynamically configures to the defined experimenttypes and their involved instrument platforms and devices, (b) ananalysis setup interface that dynamically configures to the definedcomplement and sequence of subroutines selected from an internallibrary, (c) a report setup interface that dynamically configures to thedefined report data and results complement and sequence settings, (d)design of experiments (DOE) engines that generate statistically designedexperiments correct to the defined experiment types and their involvedinstrument platforms and devices, and (e) numerical analysis, graphing,optimization, and reporting software engines that process data andresults from external software applications, instruments, devices, andICPs, execute data analysis processes according to the definedcomplement and sequence of analysis subroutines settings, and constructreports according to the defined report data and results complement andsequence settings.